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Background: The corona virus disease 2019 (COVID-19) pandemic has highlighted the fact that there are few effective antiviral agents for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Although the very recent development of vaccines is an extremely important breakthrough, it remains unclear how long-lived such vaccines will be. The development of new agents therefore remains an important goal., Purpose: Given the multifaceted pathology of COVID-19, a combinatorial formulation may provide an effective treatment. BEN815, a natural nutraceutical composed of extracts from guava leaves ( Psidium guajava ), green tea leaves ( Camellia sinensis ), and rose petals ( Rosa hybrida ), had previously shown to have a therapeutic effect on allergic rhinitis. We investigated whether BEN815 possesses anti-inflammatory, antiviral and antioxidant activities, since the combination of these effects could be useful for the treatment of COVID-19., Study Design: We examined the anti-inflammatory effects of BEN815 and its principal active components quercetin and epigallocatechin gallate (EGCG) in lipopolysaccharide (LPS)-induced RAW264.7 cells and in an LPS-challenged mouse model of endotoxemia. We also assessed the antioxidant activity, and antiviral effect of BEN815, quercetin, and EGCG in SARS-CoV-2-infected Vero cells., Methods: The principal active ingredients in BEN815 were determined and quantified using HPLC. Changes in the levels of LPS-induced pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured by ELISA. Changes in the expression levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were analyzed using western blotting. Antioxidant assay was performed using DPPH and ABTS assay. SARS-CoV-2 replication was measured by immunofluorescence staining., Results: BEN815 significantly suppressed the induction of IL-6 and TNF-α as well as COX-2 and iNOS in LPS-induced RAW264.7 cells. In addition, BEN815 protected against LPS-challenged endotoxic shock in mice. Two major constituents of BEN815, quercetin and EGCG, reduced the induction of IL-6 and TNF-α as well as COX-2 and iNOS synthase in LPS-induced RAW264.7 cells. BEN815, quercetin, and EGCG were also found to have antioxidant effects. Importantly, BEN815 and EGCG could inhibit SARS-CoV-2 replications in Vero cells., Conclusion: BEN815 is an anti-inflammatory, antiviral, and antioxidant natural agent that can be used to prevent and improve inflammation-related diseases, COVID-19., Competing Interests: We confirm that there are no conflicts of interest associated with this publication and there has no significant financial support for this work that could have influenced its outcome., (© 2021 The Authors. Published by Elsevier B.V.)

The aim of this study was to design and evaluate muco-adhesive orally disintegrating tablets manufactured by microwave irradiation and containing polysaccharide. We prepared orally disintegrating tea tablets (ODTTs) containing a 1 w/w% mass fraction of one of five polysaccharides (gum arabic, carrageenan, guar gum, tamarind gum, or pectin) and evaluated the swelling degree, tablet hardness, friability, disintegration time, and adhesive properties. All tablets had a swelling degree of about 1 mm, a hardness of over 13 N, and a friability degree of <1%. Tablets containing gum arabic and tamarind gum had disintegration times of 30 s or less and satisfied requirements as orally disintegrating tablets. This could be attributed to their high void contents, which allowed for water penetration. The adhesive properties and particle retention ratios were highest in ODTTs containing tamarind gum, which was thought to be caused by the rapid disintegration and high viscosity of the tamarind gum itself. When we investigated changing the mass fraction of tamarind gum, we found 1 w/w% was most suitable for rapid disintegration and high adhesiveness. The ODTTs containing 1 w/w% tamarind gum showed significant growth inhibition towards Streptococcus mutans . Therefore, microwave irradiation technology and addition of tamarind gum could be used to manufacture muco-adhesive orally disintegrating tablets for oral care., Competing Interests: None.

Plasma membrane Ca 2+ -ATPase (PMCA) plays a vital role in maintaining cytosolic calcium concentration ([Ca 2+ ] i ). Given that many diseases have modified PMCA expression and activity, PMCA is an important potential target for therapeutic treatment. This study demonstrates that the non-toxic, naturally-occurring polyphenol resveratrol (RES) induces increases in [Ca 2+ ] i via PMCA inhibition in primary dermal fibroblasts and MDA-MB-231 breast cancer cells. Our results also illustrate that RES and the fluorescent intracellular calcium indicator Fura-2, are compatible for simultaneous use, in contrast to previous studies, which indicated that RES modulates the Fura-2 fluorescence independent of calcium concentration. Because RES has been identified as a PMCA inhibitor, further studies may be conducted to develop more specific PMCA inhibitors from RES derivatives for potential therapeutic use.

Background: Many polyphenols have been proposed as broad-spectrum inhibitors of amyloid formation. To investigate structure-activity relationships relevant for the interaction of flavonoids with transthyretin (TTR), the protein associated with familial amyloid polyneuropathy (FAP), we compared the effects of major tea catechins and their larger polymers theaflavins, side-by-side, on TTR amyloid formation process., Methods: Interaction of flavonoids with TTR and effect on TTR stability were assessed through binding assays and isoelectric focusing in polyacrylamide gel. TTR aggregation was studied, in vitro, by dynamic light scattering (DLS), transmission electron microscopy (TEM) and in cell culture, through cytotoxicity assays., Results: Tested flavonoids bound to TTR and stabilized the TTR tetramer, with different potencies. The flavonoids also inhibited in vitro formation of TTR small oligomeric species and in cell culture inhibited pathways involving caspase-3 activation and ER stress that are induced by TTR oligomers. In all assays performed the galloyl esters presented higher potency to inhibit aggregation than the non-gallated flavonoids tested., Conclusions: Our results highlight the presence of gallate ester moiety as key structural feature of flavonoids in chemical chaperoning of TTR aggregation. Upon binding to the native tetramer, gallated flavonoids redirect the TTR amyloidogenic pathway into unstructured nontoxic aggregation assemblies more efficiently than their non-gallated forms., General Significance: Our findings suggest that galloyl moieties greatly enhance flavonoid anti-amyloid chaperone activity and this should be taken into consideration in therapeutic candidate drug discovery.